In organic chemistry, a thiol (;[ Dictionary Reference: thiol ] [ θεῖον , Henry George Liddell, Robert Scott, A Greek–English Lexicon]), or thiol derivative, is any organosulfur compound of the form , where R represents an alkyl or other organic substituent. The functional group itself is referred to as either a thiol group or a sulfhydryl group, or a sulfanyl group. Thiols are the sulfur analogue of alcohols (that is, sulfur takes the place of oxygen in the hydroxyl () group of an alcohol), and the word is a blend of " thio-" with "alcohol".
Many thiols have strong odors resembling that of garlic, cabbage or rotten eggs. Thiols are used as odorants to assist in the detection of natural gas (which in pure form is odorless), and the smell of natural gas is due to the smell of the thiol used as the odorant.
Thiols are sometimes referred to as mercaptans ()[ Dictionary Reference: mercaptan ] or mercapto compounds,[ Oxford American Dictionaries (Mac OS X Leopard).] because the thiolate group () bonds very strongly with mercury compounds.[See:
]
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On p. 13 the word "mercaptan" is coined.
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German translation: From p. 378: " … nenne ich den vom Quecksilber aufgenommenen Stoff Mercaptum (von: Corpus mercurio captum ) … " ( … I name the substance that absorbed by mercury "mercaptum" (from: the body (substance) that has been absorbed by mercury) … )
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German translation is reprinted in:
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Summarized in:
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"Mercaptan" (ethyl thiol) was discovered in 1834 by the Danish professor of chemistry William Christopher Zeise (1789–1847). He called it "mercaptan", a contraction of "corpus mercurio captans" (mercury-capturing substance) p., because it reacted violently with mercury(II) oxide ("deutoxide de mercure") p..
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The article in Annales de Chimie et de Physique (1834) was translated from the German article:
Structure and bonding
Thiols having the structure R−SH, in which an
alkyl group (R) is attached to a
sulfhydryl group (SH), are referred to as
alkanethiols or
alkyl thiols.
Thiols and alcohols have similar connectivity. Because sulfur atoms are larger than oxygen atoms, C−S
—typically around 180
Picometre—are about 40 picometers longer than typical C−O bonds. The C−S−H angles approach 90° whereas the angle for the C−O−H group is more obtuse. In solids and liquids, the
hydrogen-bonding between individual thiol groups is weak, the main cohesive force being Van der Waals interactions between the highly polarizable divalent sulfur centers.
The S−H bond is much weaker than the O−H bond as reflected in their respective bond dissociation energies (BDE). For CH3S−H, the BDE is , while for CH3O−H, the BDE is .
An S−H bond is moderately polar because of the small difference in the electronegativity of sulfur and hydrogen. In contrast, O−H bonds in hydroxyl groups are more polar. Thiols have a lower dipole moment relative to their corresponding alcohols.
Nomenclature
There are several ways to name the alkylthiols:
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The suffix -thiol is added to the name of the alkane. This method is nearly identical to naming an alcohol and is used by the IUPAC, e.g. CH3SH would be methanethiol.
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The word mercaptan replaces alcohol in the name of the equivalent alcohol compound. Example: CH3SH would be methyl mercaptan, just as CH3OH is called methyl alcohol.
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The term sulfhydryl- or mercapto- is used as a prefix, e.g. mercaptopurine.
Physical properties
Odor
Many thiols have strong
resembling that of
garlic. The odors of thiols, particularly those of low molecular weight, are often strong and repulsive. The spray of
consists mainly of low-molecular-weight thiols and derivatives.
These compounds are detectable by the human nose at concentrations of only 10 parts per billion.
Human
sweat contains (
R)/(
S)-3-methyl-3-sulfanylhexan-1-ol (3M3SH), detectable at 2 parts per billion and having an onion-like (S enantiomer) and fruity, grapefruit-like odor (R enantiomer).
(Methylthio)methanethiol (MeSCH
2SH; MTMT) is a strong-smelling volatile thiol, also detectable at parts per billion levels, found in male
mouse urine. Lawrence C. Katz and co-workers showed that MTMT functioned as a
semiochemical, activating certain mouse olfactory sensory neurons, and attracting female
Mouse.
has been shown to be required by a specific mouse olfactory receptor, MOR244-3, which is highly responsive to MTMT as well as to various other thiols and related compounds.
A human olfactory receptor, OR2T11, has been identified which, in the presence of copper, is highly responsive to the gas odorants (see below)
ethanethiol and
Tert-Butylthiol as well as other low molecular weight thiols, including
allyl mercaptan found in human
garlic breath, and the strong-smelling cyclic sulfide
thietane.
Thiols are also responsible for a class of caused by an unintended reaction between sulfur and yeast and the "skunky" odor of beer that has been exposed to ultraviolet light.
Not all thiols have unpleasant odors. For example, furan-2-ylmethanethiol contributes to the aroma of roasted coffee, whereas grapefruit mercaptan, a terpene thiol, is responsible for the characteristic scent of grapefruit. The effect of the latter compound is present only at low concentrations. The pure mercaptan has an unpleasant odor.
In the United States, natural gas distributors were required to add thiols, originally ethanethiol, to natural gas (which is naturally odorless) after the deadly New London School explosion in New London, Texas, in 1937. Many gas distributors were odorizing gas prior to this event. Most currently-used gas odorants contain mixtures of mercaptans and sulfides, with Tert-Butylthiol as the main odor constituent in natural gas and ethanethiol in liquefied petroleum gas (LPG, propane).
Boiling points and solubility
Thiols show little association by
, both with water molecules and among themselves. Hence, they have lower
and are less
soluble in water and other polar solvents than alcohols of similar molecular weight. For this reason also, thiols and their corresponding sulfide functional group isomers have similar solubility characteristics and boiling points, whereas the same is not true of alcohols and their corresponding isomeric ethers.
Bonding
The S−H bond in thiols is weak compared to the O−H bond in alcohols. For CH
3X−H, the bond enthalpies are for X = S and for X = O.
Hydrogen-atom abstraction from a thiol gives a
thiyl radical with the formula RS
•, where R = alkyl or aryl.
Characterization
Volatile thiols are easily and almost unerringly detected by their distinctive odor. Sulfur-specific analyzers for gas chromatographs are useful. Spectroscopic indicators are the
Heavy water-exchangeable S
H signal in the
Proton NMR (
33S is
NMR-active but signals for divalent sulfur are very broad and of little utility
). The
νSH band appears near 2400 cm
−1 in the
IR spectrum.
[ In the nitroprusside reaction, free thiol groups react with sodium nitroprusside and ammonium hydroxide to give a red colour.
]
Preparation
In industry, methanethiol is prepared by the reaction of hydrogen sulfide with methanol. This method is employed for the industrial synthesis of methanethiol:
- CH3OH + H2S → CH3SH + H2O
Such reactions are conducted in the presence of acidic catalysts. The other principal route to thiols involves the addition of hydrogen sulfide to Alkene. Such reactions are usually conducted in the presence of an acid catalyst or UV light. Halogen displacement, using the suitable organic halide and sodium hydrogen sulfide has also been used.[John S Roberts, "Thiols", in Kirk-Othmer Encyclopedia of Chemical Technology, 1997, Wiley-VCH, Weinheim. ]
Another method entails the alkylation of sodium hydrosulfide.
- RX + NaSH → RSH + NaX(X = Cl, Br, I)
This method is used for the production of thioglycolic acid from chloroacetic acid.
Laboratory methods
In general, on the typical laboratory scale, the direct reaction of a halogenoalkane with sodium hydrosulfide is inefficient owing to the competing formation of sulfides. Instead, alkyl halides are converted to thiols via an S-alkylation of thiourea. This multistep, one-pot process proceeds via the intermediacy of the isothiouronium salt, which is hydrolyzed in a separate step:[.]
- CH3CH2Br + SC(NH2)2 → CH3CH2SC(NH2)2Br
- CH3CH2SC(NH2)2Br + NaOH → CH3CH2SH + OC(NH2)2 + NaBr
The thiourea route works well with primary halides, especially activated ones. Secondary and tertiary thiols are less easily prepared. Secondary thiols can be prepared from the ketone via the corresponding Thioketal.[.] A related two-step process involves alkylation of thiosulfate to give the thiosulfonate ("Bunte salt"), followed by hydrolysis. The method is illustrated by one synthesis of thioglycolic acid:
- ClCH2CO2H + Na2S2O3 → NaO3S2CH2CO2H + NaCl
- NaO3S2CH2CO2H + H2O → HSCH2CO2H + NaHSO4
Organolithium compounds and react with sulfur to give the thiolates, which are readily hydrolyzed:[.]
- RLi + S → RSLi
- RSLi + HCl → RSH + LiCl
Phenols can be converted to the thiophenols via rearrangement of their O-aryl dialkylthiocarbamates.[.]
Thiols are prepared by reductive dealkylation of sulfides, especially benzyl derivatives and thioacetals.
Thiophenols are produced by S-arylation or the replacement of diazonium leaving group with sulfhydryl anion (SH−):
- + SH− → ArSH + N2
Reactions
Akin to the chemistry of alcohols, thiols form , , and , which are analogous to ethers, , and esters respectively. Thiols and alcohols are also very different in their reactivity, thiols being more easily oxidized than alcohols. Thiolates are more potent nucleophiles than the corresponding .
S-Alkylation
Thiols, or more specific their conjugate bases, are readily alkylated to give sulfides:
- RSH + R′Br + B → RSR′ + HBBr (B = base)
Acidity
Thiols are easily deprotonated.
Redox
Thiols, especially in the presence of base, are readily Redox by reagents such as bromine and iodine to give an organic disulfide (R−S−S−R).
- 2 R−SH + Br2 → R−S−S−R + 2 HBr
Oxidation by more powerful reagents such as sodium hypochlorite or hydrogen peroxide can also yield (RSO3H).
- R−SH + 3 H2O2 → RSO3H + 3 H2O
Oxidation can also be effected by oxygen in the presence of catalysts:
- 2 R–SH + O2 → RS−SR + H2O
Thiols participate in thiol-disulfide exchange:
- RS−SR + 2 R′SH → 2 RSH + R′S−SR′
This reaction is important in nature.
Metal ion complexation
With metal ions, thiolates behave as ligands to form transition metal thiolate complexes. The term mercaptan is derived from the Latin mercurium captans (capturing mercury)
Thioxanthates
Thiolates react with carbon disulfide to give thioxanthate ().
Thiyl radicals
derived from mercaptans, called , are commonly invoked to explain reactions in organic chemistry and biochemistry. They have the formula RS• where R is an organic substituent such as alkyl or aryl.
Because of the weakness of the S−H bond, thiols can function as scavengers of .
Biological importance
Cysteine and cystine
As the functional group of the proteinogenic amino acid cysteine, the thiol group plays a very important role in biology. When the thiol groups of two cysteine residues (as in monomers or constituent units) are brought near each other in the course of protein folding, an oxidation can generate a cystine unit with a disulfide bond (−S−S−). Disulfide bonds can contribute to a protein's tertiary structure if the cysteines are part of the same peptide chain, or contribute to the quaternary structure of multi-unit proteins by forming fairly strong covalent bonds between different peptide chains. A physical manifestation of cysteine-cystine equilibrium is provided by hair straightening technologies.
Sulfhydryl groups in the active site of an enzyme can form with the enzyme's substrate as well, contributing to covalent catalysis in . Active site cysteine residues are the functional unit in cysteine protease . Cysteine residues may also react with heavy metal ions (Zn2+, Cd2+, Pb2+, Hg2+, Ag+) because of the high affinity between the soft sulfide and the soft metal (see hard and soft acids and bases). This can deform and inactivate the protein, and is one mechanism of heavy metal poisoning.
Cofactors
Many cofactors (non-protein-based helper molecules) feature thiols. The biosynthesis and degradation of fatty acids and related long-chain hydrocarbons is conducted on a scaffold that anchors the growing chain through a thioester derived from the thiol coenzyme A. Dihydrolipoic acid, a dithiol, is the reduced form of lipoic acid, a cofactor in several metabolic processes in mammals.
The biosynthesis of methane, the principal hydrocarbon on Earth, arises from the reaction mediated by coenzyme M (2-mercaptoethyl sulfonic acid) and coenzyme B (7-mercaptoheptanoylthreoninephosphate). Thiolates, the conjugate bases derived from thiols, form strong complexes with many metal ions, especially those classified as soft. The stability of metal thiolates parallels that of the corresponding sulfide minerals.
Drugs
Drugs containing thiol group:
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6-Mercaptopurine (anticancer)
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Captopril (antihypertensive)
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D-penicillamine (antiarthritic)
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Sodium aurothiolate (antiarthritic)
In skunks
The defensive spray of skunks consists mainly of low-molecular-weight thiols and derivatives with a foul odor, which protects the skunk from predators. Owls are able to prey on skunks, as they lack a sense of smell.
Examples of thiols
See also
External links
